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Indene derivatives and process for the preparation thereof
7741323 Indene derivatives and process for the preparation thereof
Patent Drawings:

Inventor: Cheon, et al.
Date Issued: June 22, 2010
Application: 10/599,911
Filed: April 13, 2005
Inventors: Cheon; Hyae Gyeong (Daejeon, KR)
Yoo; Sung-Eun (Kongju-si, KR)
Kim; Sung Soo (Daejeon, KR)
Yang; Sung-Don (Daejeon, KR)
Kim; Kwang-Rok (Daejeon, KR)
Rhee; Sang Dal (Daejeon, KR)
Ahn; Jin Hee (Daejeon, KR)
Kang; Seung Kyu (Daejeon, KR)
Jung; Won Hoon (Daejeon, KR)
Park; Sung Dae (Seoul, KR)
Kim; Nam Gee (Seoul, KR)
Lee; Jang Hyuk (Yongin-si, KR)
Huh; Sun Chul (Koyang-si, KR)
Lee; Jae Mok (Seoul, KR)
Song; Seog Beom (Suwon-si, KR)
Kwon; Soon Ji (Yongin-si, KR)
Kim; Jong Hoon (Anyang-si, KR)
Lee; Jeong-Hyung (Daejeon, KR)
Kim; Seung Jun (Daejeon, KR)
Assignee:
Primary Examiner: Anderson; Rebecca L
Assistant Examiner: Coughlin; Matthew P
Attorney Or Agent: Baker & Hostetler, LLP
U.S. Class: 514/238.2; 514/231.5; 514/351; 514/357; 514/365; 514/400; 514/438; 514/443; 514/463; 514/466; 514/471; 514/510; 514/619; 514/640; 514/644; 544/159; 544/165; 544/177; 544/399; 546/300; 546/335; 546/337; 546/338; 548/204; 548/336.1; 549/433; 549/442; 549/496; 549/58; 549/65; 549/77; 558/426; 564/300; 564/301
Field Of Search: 564/300; 564/301
International Class: C07C 255/47; A61K 31/277; A61K 31/216; A61K 31/165; C07D 413/12; C07D 333/28; C07D 333/22; C07D 317/70; C07D 307/54; C07D 277/30; C07D 265/30; C07D 295/135; C07D 233/64; C07D 213/53; C07D 213/64; A61K 31/5377; A61K 31/495; A61K 31/4402; C07C 251/32; C07C 237/24; C07C 69/74; A61K 31/44; A61K 31/426; A61K 31/4164; A61K 31/381; A61K 31/36; C07D 333/24; C07D 333/60; C07D 317/60
U.S Patent Documents:
Foreign Patent Documents:
Other References: Golub et al., Science, vol. 286, Oct. 15, 1999, pp. 531-537. cited by examiner.
Shearer and Billin, Biochimica et Biophysica Acta 2007, 1771, 1082-1093. cited by examiner.
Hussain et al., Diabetes Research and Clinical Practice 2007, 76, 317-326. cited by examiner.
Mugnier et al. J. Org. Chem. 1993, 58, 5329-5334. cited by examiner.
Ahn et al. J. Med. Chem. 2006, 49, 4781-4784. cited by examiner.
Jordan, V. C. Nature Reviews: Drug Discovery, 2, 2003, pp. 205-213. cited by examiner.









Abstract: An indene derivative for selectively modulating the activities of peroxisome proliferator activated receptors (PPARs) having the following formula (I): ##STR00001## wherein, R.sub.1 is C.sub.1-6 alkyl, C.sub.1-6 alkenyl, or C.sub.3-6 cycloalkyl, each of which is unsubstituted or substituted with one or more phenyl groups; R.sub.2 is H, CN, CO.sub.2R.sup.a, CH.sub.2CO.sub.2R.sup.a, CONR.sup.bR.sup.c, ##STR00002## or phenyl; R.sub.3 is C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, naphthyl, phenyl, ##STR00003## being each unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, CN, NH.sub.2, NO.sub.2, OR.sup.a, phenyloxy, C.sub.1-6 alkyl, and C.sub.3-6 cycloalkyl; and R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently H, OH, OSO.sub.2CH.sub.3, O(CH.sub.2).sub.mR.sup.e, CH.sub.2R.sup.f, OCOCH.sub.2OR.sup.g, OCH.sub.2CH.sub.2OR.sup.g, OCH.sub.2CH.dbd.CHR.sup.g, or pyridine-2-yloxy, or R.sub.5 and R.sub.6 together form OCH.sub.2O.
Claim: What is claimed is:

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof: ##STR00126## wherein, R.sub.1 is C.sub.1-6 alkyl, C.sub.1-6 alkenyl, or C.sub.3-6 cycloalkyl, eachof which is unsubstituted or substituted with one or more phenyl groups; R.sub.2 is H, CN, CO.sub.2R.sup.a, CH.sub.2CO.sub.2R.sup.a, CONR.sup.bR.sup.c, ##STR00127## or phenyl; R.sub.3 is C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, naphthyl, phenyl,##STR00128## being each unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, CN, NH.sub.2, NO.sub.2, OR.sup.a, phenyloxy, C.sub.1-6 alkyl, and C.sub.3-6 cycloalkyl; and R.sub.4, R.sub.5, R.sub.6, andR.sub.7 are each independently H, OH, OSO.sub.2CH.sub.3, O(CH.sub.2).sub.mR.sup.e, CH.sub.2R.sup.f, OCOCH.sub.2OR.sup.g, OCH.sub.2CH.sub.2OR.sup.g, OCH.sub.2CH.dbd.CHR.sup.g, or R.sub.5 and R.sub.6 together form OCH.sub.2O; in which R.sup.a is H,C.sub.1-6 alkyl, or C.sub.3-6 cycloalkyl, C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl being each unsubstituted or substituted with one or more halogens; R.sup.b and R.sup.c are each independently H, C.sub.1-6 alkyl, or C.sub.3-6 cycloalkyl; R.sup.d is O,S, or NR.sup.a; R.sup.e is H, halogen, C.sub.3-6 cycloalkyl, naphthyl, ##STR00129## or phenyl, phenyl being unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, CN, NH.sub.2, NO.sub.2, OR.sup.a,CF.sub.3, and COOR.sup.a; R.sup.f is OCH.sub.2CH.sub.2R.sup.g or ##STR00130## R.sup.g is phenyl, which is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, CN, NH.sub.2, NO.sub.2, and OR.sup.a; and m is an integer in the range of 1 to 5.

2. The compound of claim 1, wherein R.sub.1 is C.sub.1-6 alkyl, which is unsubstituted or substituted with a phenyl group; R.sub.2 is H, CN, CO.sub.2R.sup.a, CH.sub.2CO.sub.2R.sup.a, CONR.sup.bR.sup.c, or phenyl; R.sub.3 is C.sub.1-6 alkyl,C.sub.3-6 cycloalkyl, phenyl, ##STR00131## phenyl being unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, C.sub.1-6 alkyl, and C.sub.3-6 cycloalkyl; R.sub.4 and R.sub.7 are H; R.sub.5 and R.sub.6are each independently OH, OSO.sub.2CH.sub.3, O(CH.sub.2).sub.mR.sup.e, CH.sub.2R.sup.f, OCOCH.sub.2OR.sup.g, OCH.sub.2CH.sub.2OR.sup.g, or OCH.sub.2CH.dbd.CHR.sup.g, or together form OCH.sub.2O; R.sup.a is H or C.sub.1-6 alkyl; R.sup.d is O orNCH.sub.3; R.sup.e is H, halogen, C.sub.3-6 cycloalkyl, naphthyl, ##STR00132## or phenyl, phenyl being unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, OH, methoxy, CF.sub.3, and COOR.sup.a; R.sup.f is OCH.sub.2CH.sub.2R.sup.g or ##STR00133## and R.sup.g is phenyl.

3. The compound of claim 2, wherein R.sub.1 is CH.sub.3; R.sub.2 is H, CN, CO.sub.2R.sup.a, or CONR.sup.bR.sup.c; R.sub.3 is C.sub.1-6 alkyl, phenyl, ##STR00134## phenyl being unsubstituted or substituted with one or more halogens orC.sub.1-6 alkyl groups; and R.sub.5 and R.sub.6 are each independently O(CH.sub.2).sub.mR.sup.e or CH.sub.2R.sup.f, or together form OCH.sub.2O.

4. A compound selected from the group consisting of: 1) 6-methoxy-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-carboxylate ethyl ester 2) 1-(trans-isopropylimino-N-oxy)-6-methoxy-3-phenyl-1H-indene-2-carboxylate ethyl ester 3)1-(trans-benzylimino-N-oxy)-6-methoxy-3-phenyl-1H-indene-2-carboxylate ethyl ester 4) 1-(trans-ethylimino-N-oxy)-6-methoxy-3-phenyl-1H-indene-2-carboxylate ethyl ester 5) 6-methoxy-1-(trans-phenylpropylimino-N-oxy)-3-phenyl-1H-indene-2-carboxyl- ateethyl ester 6) 6-methoxy-1-(trans-(2-methylbutenylimino)-N-oxy)-3-phenyl-1H-indene-2-car- boxylate ethyl ester 7) 1-(trans-isobutylimino-N-oxy)-6-methoxy-3-phenyl-1H-indene-2-carboxylate ethyl ester 8)1-(trans-methylimino-N-oxy)-6-(2-morphorline-4-ylethoxy)-3-phenyl-1H-inde- ne-2-carboxylate ethyl ester 9) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb- oxylate ethyl ester 10)1-(trans-methylimino-N-oxy)-6-phenetyloxy-3-phenyl-1H-indene-2-carboxylat- e ethyl ester 11) 3-furan-3-yl-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-indene-2-- carboxylate ethyl ester 12)6-hydroxy-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-carboxylate ethyl ester 13) 1-(cis-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carbox- ylate ethyl ester 14) 3-(trans-methylimino-N-oxy)-1-phenyl-3H-indene-5-ol 15)1-(trans-methylimino-N-oxy)-3-phenyl-6-(5-phenylpentyloxy)-1H-indene-- 2-carboxylate ethyl ester 16) 1-(cis-methylimino-N-oxy)-3-phenyl-6-(5-phenylpentyloxy)-1H-indene-2-carb- oxylate ethyl ester 17)6-[2-(4-chlorophenoxy)acetoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1H-in- dene-2-carboxylate ethyl ester 18) 6-[2-(4-chlorophenoxy)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1H-ind- ene-2-carboxylate ethyl ester 19)1-(trans-methylimino-N-oxy)-6-(naphthalene-2-ylmethoxy)-3-phenyl-1H-inden e-2-carboxylate ethyl ester 20) methyl-[3-phenyl-6-(3-phenylpropoxy)indene-1-yllidene]amine-N-oxide 21) 1-(trans-methylimino-N-oxy)-6-[2-(5-methyl-2-phenylthiazol-4-yl)ethoxy]-3--phenyl-1H-indene-2-carboxylate ethyl ester 22) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb- oxylate ethyl ester 23) 6-[2-(4-hydroxyphenyl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1H-ind- ene-2-carboxylate ethyl ester24) 6-(2-adaman-1-ylethoxy)-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-- carboxylate ethyl ester 25) 6-(2-cyclohexylethoxy)-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-c- arboxylate ethyl ester 26)1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylprophenoxy)-1H-indene-2-c- arboxylate ethyl ester 27) 6-[2-(2-fluorophenyl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1H-inde- ne-2-carboxylate ethyl ester 28)6-[2-(3-fluorophenyl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1H-inde- ne-2-carboxylate ethyl ester 29) 6-[2-(4-fluorophenyl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1H-inde- ne-2-carboxylate ethyl ester 30)1-(trans-methylimino-N-oxy)-3-phenyl-6-[2-(3-trifluoromethylphenyl)ethoxy- ]-1H-indene-2-carboxylate ethyl ester 31) 6-(4-methoxycarbonylbenzyloxy)-1-(trans-methylimino-N-oxy)-3-phenyl-1H-in- dene-2-carboxylate ethyl ester 32)1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb- oxylate ethyl amide 33) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate ethyl ester 34)6-[2-(cyclohexylmethylamino)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-- 1H-indene-2-carboxylate ethyl ester 35) 3-(2-fluorophenyl)-6-methoxy-1-(trans-methylimino-N-oxy)-1H-indene-2-carb- oxylate ethyl ester 36)1-(trans-methylimino-N-oxy)-6-[2-(4-methylpiperazine-1-yl)ethoxy]-3-pheny- l-1H-indene-2-carboxylate ethyl ester 37) (2,3-diphenyl indene-1-yl lidene)methylamine-N-oxide 38) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb-oxylate isopropyl amide 39) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb- oxylate cyclohexyl amide 40) [1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-yl]- morpholine-4-yl-methanone 41)1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-yl-ethoxy)-3-phenyl-1H-inde- ne-2-carboxylate cyclohexyl amide 42) 1-(trans-methylimino-N-oxy)-3-phenyl-5-(3-phenylpropoxy)-1H-indene-2-carb- oxylate ethyl ester 43)1-(trans-methylimino-N-oxy)-6-phenethyloxymethyl-3-phenyl-1H-indene-2-car- boxylate ethyl ester 44) (6-methoxy-3-phenylindene-1-yllidene)methylamine-N-oxide 45) 1-(cis-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-indene-- 2-carboxylateethyl ester 46) 6-(2-bromoethoxy)-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-carbox- ylate ethyl ester 47) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate tert-buthyl ester 48)1-(trans-methylimino-N-oxy)-5,6-methylenedioxy-1-oxo-3-phenyl-1H-indene-2- -carboxylate ethyl ester 49) 4-[2-isopropylcarbamoyl-3-(trans-methylimino-N-oxy)-1-phenyl-3H-indene-5-- yl-oxylmethyl]benzoate methyl ester 50)1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate isopropyl amide 51) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate cyclopropyl amide 52)3-(3-fluorophenyl)-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy- )-1H-indene-2-carboxylate isopropyl amide 53) (6-methoxy-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-yl)acetate ethyl ester 54)(6-methoxy-1-(cis-methylimino-N-oxy)-3-phenyl-1H-indene-2-yl)acetate ethyl ester 55) 5-[2-(5-ethylpyridine-2-yl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1- H-indene-2-carboxylate isopropyl amide 56)1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-3-p-tolyl-1H-indene-2-car- boxylate ethyl ester 57) 1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-3-thiophene-2-yl-1H-inden- e-2-carboxylate ethyl ester 58)3-(4-chlorophenyl)-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-ind- ene-2-carboxylate ethyl ester 59) 3-(5-chlorothiophene-2-yl)-1-(trans-methylimino-N-oxy)-6-(3-phenyl propoxy)-1H-indene-2-carboxylate ethyl ester 60)1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-3-m-tolyl-1H-indene-2-car- boxylate ethyl ester 61) 1-(trans-methylimino-N-oxy)-3-(4-phenoxyphenyl)-6-(3-phenylpropoxy)-1H-in- dene-2-carboxylate ethyl ester 62)3-benzo-[1,3]-dioxol-5-yl-1-(trans-methylimino-N-oxy)-6-(3-phenyl propoxy)-1H-indene-2-carboxylate ethyl ester 63) methyl-[6-(3-phenylpropoxy)-3-pyridine-2-yl-indene-1-yllindene]-amine-N-o- xide 64)3-furan-2-yl-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-i- ndene-2-carboxylate ethyl ester 65) 3-ethyl-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-indene-2-carbo- xylate ethyl ester 66)3-methyl-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-indene-2-carb- oxylate ethyl ester 67) 1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-3-thiophene-3-yl-1H-inden- e-2-carboxylate ethyl ester 68)3-cyclopropyl-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-indene-2- -carboxylate ethyl ester 69) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-thiophene-3-yl-- 1H-indene-2-carboxylate ethyl ester 70)3-benzo-[b]-thiophene-3-yl-1-(trans-methylimino-N-oxy)-6-(3-phenyl propoxy)-1H-indene-2-carboxylate ethyl ester 71) 3-(1H-imidazole-4-yl)-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-- indene-2-carboxylate ethyl ester 72) 3-(1-ethylpropyl)-1-(trans-methylimino-N-oxy)-6-(3-phenylpropoxy)-1H-indene-2-carbo- xylate ethyl ester 73) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb- oxylate amide 74)6-(4-benzylmorpholine-2-ylmethoxy)-1-(trans-methylimino-N-oxy)-3-phenyl-1- H-indene-2-carboxylate isopropyl amide 75) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(3-phenylpropoxy)-1H-indene-2-carb- onitrile 76)1-(trans-methylimino-N-oxy)-5,6-methylenedioxy-1-oxo-3-phenyl-1H-phenyl-2- -carboxylate isopropyl amide 77) 1-(trans-methylimino-N-oxy)-6-morpholine-4-ylmethyl-3-phenyl-1H-indene-2-- carboxylate ethyl ester 78)1-(trans-methylimino-N-oxy)-3-phenyl-6-(2-pyridine-2-ylethoxy)-1H-indene-- 2-carboxylate ethyl ester 79) 6-[2-(5-ethylpyridine-2-yl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1- H-indene-2-carboxylate ethyl ester 80)1-(trans-methylimino-N-oxy)-3-phenyl-6-(2-pyridine-2-ylethoxy)-1H-indene-- 2-carboxylate isopropyl amide 81) 6-[2-(5-ethylpyridine-2-yl)ethoxy]-1-(trans-methylimino-N-oxy)-3-phenyl-1- H-indene-2-carboxylate isopropyl amide 82)methyl-[6-(2-morpholine-4-ylethoxy)-3-phenylindene-1-yllidene]amine-N-oxi- de 83) 5,6-bis-methanesulfonyloxy-1-(trans-methylimino-N-oxy)-3-phenyl-1H-- indene-2-carboxylate ethyl ester 84)1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate isobutyl ester 85) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate methyl ester 86)1-(cis-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-indene-- 2-carboxylate methyl ester 87) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate propyl ester 88)3-(4-fluorophenyl)-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy- )-1H-indene-2-carboxylate ethyl ester 89) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(pyridine-2-ylmethoxy)-1H-indene-2- -carboxylate ethyl ester 90)1-(trans-methylimino-N-oxy)-3-phenyl-6-(pyridine-2-yloxy)-1H-indene-2-car- boxylate ethyl ester 91) 6-(3-methoxybenzyloxy)-1-(trans-methylimino-N-oxy)-3-phenyl-1H-indene-2-c- arboxylate ethyl ester 92)1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-thiophene-3-yl-- 1H-indene-2-carboxylate isopropyl amide 93) 3-(1-ethylpropyl)-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-yl ethoxy)-1H-indene-2-carboxylate ethyl ester 94)3-benzo-[b]-thiophene-3-yl-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-- ylethoxy)-1H-indene-2-carboxylate isopropyl amide 95) 3-(4-fluorophenyl)-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy- )-1H-indene-2-carboxylate isopropyl amide 96)3-(1-ethylpropyl)-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)- -1H-indene-2-carboxylate isopropyl amide 97) 1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-(2,4,6-trimethy- l phenyl)-1H-indene-2-carboxylate ethyl ester 98)3-(2,6-dimethylphenyl)-1-(trans-methylimino-N-oxy)-6-(2-morpholine-4-ylet- hoxy)-1H-indene-2-carboxylate ethyl ester 99) 1-(trans-methylimino-N-oxy)-3-phenyl-5-(2-pyridine-2-ylethoxy)-1H-indene-- 2-carboxylate isopropyl amide 100)1-(trans-methylimino-N-oxy)-5-(2-morpholine-4-ylethoxy)-3-phenyl-1H-inden- e-2-carboxylate isopropyl amide 101) 1-(cis-methylimino-N-oxy)-6-(2-morpholine-4-ylethoxy)-3-phenyl-1H-indene-- 2-carboxylate isopropyl ester 102)3-(3-fluorophenyl)-1-(trans-methylimino-N-oxy)-6-(2-pyridine-2-ylethoxy)-- 1H-indene-2-carboxylate isopropyl amide 103) 6-[2-(5-ethylpyridine-2-yl)ethoxy]-3-(3-fluorophenyl)-1-(trans-methylimin- o-N-oxy)-1H-indene-2-carboxylate isopropyl amide 104)3-(4-cyanophenyl)-6-(2-morpholine-4-ylethoxy)-1-(trans-methylimino-N-oxy)- -1H-indene-2-carboxylate ethyl ester, and 105) 1-(trans-methylimino-N-oxy)-3-phenyl-6-(2-pyridine-2-ylethoxy)-1H-indene-- 2-carboxylate isopropyl ester.

5. A process for preparing the compound of formula (I) which comprises the step of subjecting an indenone compound of formula (II) to a condensation reaction with R.sub.1NHOH to obtain a compound of formula (I); or comprises the steps ofsubjecting an indenone compound of formula (II) to a condensation reaction with NH.sub.2OH to obtain a compound of formula (III), and conducting a reaction of the compound of formula (III) with R.sub.1X to obtain a compound of formula (I): ##STR00135##wherein, X is halogen; R.sub.1 is C.sub.1-6 alkyl, C.sub.1-6 alkenyl, or C.sub.3-6 cycloalkyl, each of which is unsubstituted or substituted with one or more phenyl groups; R.sub.2 is H, CN, CO.sub.2R.sup.a, CH.sub.2CO.sub.2R.sup.a, CONR.sup.bR.sup.c,##STR00136## or phenyl; R.sub.3 is C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, naphthyl, phenyl, ##STR00137## phenyl and ##STR00138## being each unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, CN,NH.sub.2, NO.sub.2, OR.sup.a, phenyloxy, C.sub.1-6 alkyl, and C.sub.3-6 cycloalkyl; and R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are each independently H, OH, OSO.sub.2CH.sub.3, O(CH.sub.2).sub.mR.sup.e, CH.sub.2R.sup.f, OCOCH.sub.2OR.sup.g,OCH.sub.2CH.sub.2OR.sup.g, OCH.sub.2CH.dbd.CHR.sup.g, R.sub.5 and R.sub.6 together form OCH.sub.2O; in which R.sup.a is H, C.sub.1-6 alkyl, or C.sub.3-6 cycloalkyl, C.sub.1-6 alkyl and C.sub.3-6 cycloalkyl being each unsubstituted or substituted withone or more halogens; R.sup.b and R.sup.c are each independently H, C.sub.1-6 alkyl, or C.sub.3-6 cycloalkyl; R.sup.d is O, S, or NR.sup.a; R.sup.e is H, halogen, C.sub.3-6 cycloalkyl, naphthyl, ##STR00139## or phenyl, phenyl being unsubstituted orsubstituted with one or more substituents selected from the group consisting of halogen, CN, NH.sub.2, NO.sub.2, OR.sup.a, CF.sub.3, and COOR.sup.a; R.sup.f is OCH.sub.2CH.sub.2R.sup.g or ##STR00140## R.sup.g is phenyl, which is unsubstituted orsubstituted with one or more substituents selected from the group consisting of halogen, CN, NH.sub.2, NO.sub.2, and OR.sup.a; and m is an integer in the range of 1 to 5.

6. The process of claim 5, wherein the indenone compound of formula (II) is prepared by a process comprising the steps of: 1) reacting compounds of formula (V) and (VI) to obtain a compound of formula (VII); 2) subjecting the compound offormula (VII) to cyclization to obtain a compound of formula (VIII); and 3) subjecting the compound of formula (VIII) to oxidation, ##STR00141## wherein, R.sub.2 to R.sub.7 have the same meanings as defined in claim 5, and Z is halogen or activatedleaving group.

7. The process of claim 5, wherein the indenone compound of formula (II) is prepared by a process comprising the steps of: 1) reacting compounds of formula (IX) and (X) to obtain a compound of formula (XI); 2) subjecting the compound offormula (XI) to cyclization to obtain a compound of formula (XII); and 3) subjecting the compound of formula (XII) to oxidation, ##STR00142## wherein, R.sub.2 to R.sub.7 have the same meanings as defined in claim 5.

8. The process of claim 5, wherein the indenone compound of formula (II) is prepared by a process comprising the steps of: 1) reacting compounds of formula (IX) and (XIII) to obtain a compound of formula (XIV); and 2) subjecting the compoundof formula (XIV) to cyclization, ##STR00143## wherein, R.sub.2 to R.sub.7 have the same meanings as defined in claim 5.

9. The process of claim 5, wherein the indenone compound of formula (II) is prepared by a process comprising the steps of: 1) subjecting a compound of formula (XV) to bromination obtain a compound of formula (XVI); and 2) subjecting thecompound of formula (XVI) to a carbon-carbon coupling reaction in the presence of a metal catalyst, or to a substitution reaction using a nucleophile, ##STR00144## wherein, R.sub.3 to R.sub.7 have the same meanings as defined in claim 5.

10. The process of claim 5, wherein the indenone compound of formula (II) is prepared by a process comprising the steps of: 1) subjecting a compound of formula (XVII) to bromination to obtain a compound of formula (XVIII); and 2) subjectingthe compound of formula (XVIII) to a carbon-carbon coupling reaction in the presence of a metal catalyst, or to a substitution reaction using a nucleophile, ##STR00145## wherein, R.sub.2 and R.sub.4 to R.sub.7 have the same meanings defined in claim 5.

11. The process of claim 5, wherein the indenone compound of formula (II) is prepared by subjecting a compound of formula (XIX) to an acylation reaction, a halogenation reaction followed by a substitution reaction by a nucleophile, or acarbon-carbon coupling reaction in the presence of a metal catalyst, ##STR00146## wherein, R.sub.2 and R.sub.3 have the same meanings defined in claim 5, Y is hydroxy, thiol, amino C.sub.1-6 alkyl or halogen, and n is an integer in the range of 0 to 5.

12. A pharmaceutical composition for activating the activities of peroxisome proliferator activated receptor gamma sub type comprising the compound or salt defined in claim 1 as an active ingredient together with a pharmaceutically acceptablecarrier.
Description:
 
 
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